EVEROLIMUS APPROVED FOR BREAST CANCER IN EUROPE 

July 31, 2012 — The European Commission has approved everolimus (Afinitor, Novartis) for use with exemestane (Aromasin, Pfizer) to treat postmenopausal women with advanced breast cancer, according to a Novartis Oncology press release. The indication is for the treatment of hormone-receptor-positive, HER2-negative breast cancer after progression on an aromatase inhibitor.

This news comes less than 2 weeks after the US Food and Drug Administration approved everolimus for the same indication, as reported by Medscape Medical News.

This is "an important milestone, marking the first major advance for women in the European Union with hormone-receptor-positive advanced breast cancer since the introduction of aromatase inhibitors more than 15 years ago," said Hervé Hoppenot, president of Novartis Oncology, in the press release. Everolimus provides "a new option in the battle against this advanced form of breast cancer, where there remains a significant unmet need," he added.

The approval was based on the phase 3 Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2). In that randomized multicenter study of 724 patients, local investigator assessment showed that the addition of everolimus to exemestane more than doubled median progression-free survival — to 7.8 months from 3.2 months with exemestane alone (hazard ratio, 0.45; 95% confidence interval, 0.38 to 0.54; P < .0001).

Another analysis, based on independent central radiology, also showed that the combined treatment extended median progression-free survival — to 11.0 months from 4.1 months with exemestane alone (hazard ratio, 0.38; 95% CI, 0.31 to 0.48; P < .0001).

The most common grade 3/4 adverse reactions (incidence of 2% or more) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis, and diarrhea.

"Everolimus is the most important advance in breast cancer since trastuzumab," said Fabrice André, MD, from the Institut Gustave Roussy, Paris, France, when the results of a preplanned interim analysis of BOLERO-2 were reported at the 2011 European Multidisciplinary Cancer Congress. He acted as discussant of the trial at the time.

However, when updated findings from the trial were reported later in 2011 at the 34th Annual San Antonio Breast Cancer Symposium, another expert had some more tempered comments about the drug.

The rate of response to the combination therapy in BOLERO-2 was low, at 12%, said Harold Burstein, MD, from the division of breast oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts, who was not involved in the study. He did not describe the trial results as practice changing at the time.

However, coprincipal investigator of BOLERO-2, José Baselga, MD, from the Massachusetts General Hospital and Harvard Medical School in Boston, has been repeatedly effusive about the results of the trial.

The combination of everolimus plus exemestane has produced "the strongest data ever seen in estrogen-receptor-positive breast cancer," he told Medscape Medical News when results from the interim analysis were presented.

"Everolimus is the first agent to enhance hormone therapy in refractory ER-positive breast cancer patients," and the results of the trial represent a "paradigm shift in the management of these patients," he said at the time.

Everolimus, "the first mTOR inhibitor to be approved for this disease, has the potential to redefine the way this common form of advanced breast cancer is treated," Dr. Baselga states in the Novartis Oncology press release announcing the approval of everolimus by the European Commission.